PROJECT SUMMARY/ABSTRACT Though the use of HT7 acupuncture has been shown to reduce drug-seeking behavior, there are several barriers limiting its effectiveness. These include, pragmatically, the number and frequency of treatments required, patient adherence in light of high demands on time and resources and incomplete understanding of its underlying mechanisms. More knowledge and novel methods are needed to reduce these burdens and improve outcomes. A portion of the neurological pathway mediating these effects begins with activation of peripheral mechanoreceptors, which effect, after several synapses, the mesolimbic system. The aforementioned pathway forms the scientific premise of this proposal. We aim to test and define the mechanism of action of two novel methods of administering acupuncture; they are 1) subcutaneous vibratory implants and 2) optogenetic stimulation of peripheral mechanoreceptors. The overall hypothesis is that stimulation of peripheral mechanoreceptors, Meissner?s and Pacinian Corpuscles, via vibration or optogenics, will alter the mesolimbic activity and produce changes in the effects of acute cocaine administration. Further, that the effects will be reversed by ablation of the DCML pathway and/or administration (systemic or local) of naltrindole. This project allows the applicant exposure to important investigative techniques and seasoned researchers in the area of acupuncture and alternative medicine to facilitate a successful transition from clinical practice to full-time independent research. These include, in- vivo electrophysiology, fast-scan cyclic voltammetry, microdialysis, behavioral assays associated with drug seeking, optogenetics and access to on-site training in the labs of Scott Steffensen (BYU), Hee Young Kim (Daegu Haany University) and Jiang Ye (Rutgers). These laboratories have established themselves as leaders in this field and are ideally suited to provide world-class training. This project also meets several items of the NCCIH strategic plan, namely, to develop new research methods to improve understanding of complimentary healthcare approaches and hard-to-care for symptoms and to train clinician-scientists in the area of complimentary and integrative health research.